ArticlePloS one2009
Cystatin C is downregulated in prostate cancer and modulates invasion of prostate cancer cells via MAPK/Erk and androgen receptor pathways.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- The relationship between preoperative serum cystatin C levels and postoperative oncologic outcomes in patients with renal cell carcinoma: a systematic review and meta-analysis of 1641 patients.Updates in surgery · 2025Pooled it
- Exceptional and typical biomarker responses to AminoTriComplex in metastatic prostate cancer: a case series.Journal of medical case reports · 2026Article
- Urinary biomarkers in metastatic bone pain: Results from a multicentre randomized trial of ibandronate compared to single dose radiotherapy for localized metastatic bone pain in prostate cancer (RIB).Journal of bone oncology · 2024Article
- The 'other' big complication: how chronic kidney disease impacts on cancer risks and outcomes.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Review
- Prebiopsy bpMRI and hematological parameter-based risk scoring model for predicting outcomes in biopsy-naive men with PSA 4-20 ng/mL.Scientific reports · 2022Article
- Inflammatory serum factors from aortic valve stenosis patients modulate sex differences in valvular myofibroblast activation and osteoblast-like differentiation.Biomaterials science · 2022Article
- Testis-specific protein Y-encoded 1 regulates androgen receptor expression through the MAPK/ERK pathway in male hepatocellular carcinoma.Saudi medical journal · 2022Article
- Role of cystatin C in urogenital malignancy.Frontiers in endocrinology · 2022Review
- Cystatin C and cystatin SN as possible soluble tumor markers in malignant uveal melanoma.Radiology and oncology · 2021Article
- Externally added cystatin C reduces growth of A375 melanoma cells by increasing cell cycle time.FEBS open bio · 2021Article
- Prognostic Value of Pretreatment Serum Cystatin C Level in Nasopharyngeal Carcinoma Patients in the Intensity-modulated Radiotherapy Era.OncoTargets and therapy · 2021Article
- Correlation between prostate-specific antigen and four renal function-associated parameters in different ethnicities in southwest China.Experimental and therapeutic medicine · 2020Article
- Cytokines secreted by stromal cells in TNBC microenvironment as potential targets for cancer therapy.Cancer biology & therapy · 2020Article
- Article
- The Role of Cysteine Cathepsins in Cancer Progression and Drug Resistance.International journal of molecular sciences · 2019Review
- Aberrant cystatin-C expression in blood from patients with breast cancer is a suitable marker for monitoring tumor burden.Oncology letters · 2018Article
- ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Cystatin C takes part in melanoma-microglia cross-talk: possible implications for brain metastasis.Clinical & experimental metastasis · 2018Article
- Identification of Potential Prostate Cancer-Related Pseudogenes Based on Competitive Endogenous RNA Network Hypothesis.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Cystatin A suppresses tumor cell growth through inhibiting epithelial to mesenchymal transition in human lung cancer.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystatin C is believed to prevent tumor progression by inhibiting the activities of a family of lysosomal cysteine proteases. However, little is known about the precise mechanism of cystatin C function in prostate cancer. In the present study, we examined the expression of cystatin C and its association with matrix metalloproteinases 2 (MMP2) and androgen receptor (AR) in a tissue microarray comparing benign and malignant specimens from 448 patients who underwent radical prostatectomy for localized prostate cancer. Cystatin C expression was significantly lower in cancer specimens than in benign tissues (p<0.001) and there was a statistically significant inverse correlation between expression of cystatin C and MMP2 (r(s) (2) = -0.056, p = 0.05). There was a clear trend that patients with decreased level of cystatin C had lower overall survival. Targeted inhibition of cystatin C using specific siRNA resulted in an increased invasiveness of PC3 cells, whereas induction of cystatin C overexpression greatly reduced invasion rate of PC3 in vitro. The effect of cystatin C on modulating the PC3 cell invasion was provoked by Erk2 inhibitor that specifically inhibited MAPK/Erk2 activity. This suggests that cystatin C may mediate tumor cell invasion by modulating the activity of MAPK/Erk cascades. Consistent with our immunohistochemical findings that patients with low expression of cystatin C and high expression of androgen receptor (AR) tend to have worse overall survival than patients with high expression of cystatin C and high AR expression, induced overexpression of AR in PC3 cells expressing cystatin C siRNA greatly enhanced the invasiveness of PC3 cells. This suggests that there may be a crosstalk between cystatin C and AR-mediated pathways. Our study uncovers a novel role for cystatin C and its associated cellular pathways in prostate cancer invasion and metastasis.
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